P53 activation promotes MCL1 degradation through downregulating the RAS/RAF/MEK/ERK signaling pathway, therefore, MDM2 inhibitor in combination with BCL2 inhibitor overcomes MCL1-mediated apoptotic resistance and shows synergistic lethality of relapsed/refractory AML in preclinical and clinical trials (115) (Table 1). This evidence concerns the gene TP53 and acute myeloid leukemia.